Differential Activation of Leukotriene Biosynthesis by Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin-5 in an Eosinophilic Substrain of HL-60 Cells

Abstract

Cytokines can stimulate eosinophils to produce cysteinyl leukotrienes (LTs) in the lung that provoke tissue destruction associated with asthma. Priming of an eosinophilic substrain of HL-60 cells (HL-60#7) with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) before ionophore challenge was found to produce an apparent 45% increase in total LT production in a dose-dependent manner (ED50 = 150 pmol/L) that could be accounted for by a decrease in the time required for maximal formation of LTs. GM-CSF had no effect on the kinetic parameters of LTC4 synthase and therefore probably acts upstream of this catalytic event. Incubation with interleukin-5 (IL-5), however, had no effect on LT biosynthesis. This differential priming ability was not a consequence of different receptor populations or differences in the affinity or stability of the ligand-receptor complexes of GM-CSF and IL-5. GM-CSF and IL-5 each displayed similar populations of high-affinity binding sites and neither GM-CSF nor IL-5 were able to cross-compete for the other's receptor binding sites. Analysis of phosphotyrosine patterns suggest that IL-5 is incapable of transducing a signal in eosinophilic HL-60#7 cells even though IL-5 and GM-CSF receptors mediate signal transduction via a common β-chain component that is also necessary for high-affinity binding. Overall, this unique system may permit the dissection of distinct events responsible for specific intracellular signals transduced separately by GM-CSF or IL-5. © 1995 by The American Society of Hematology.